Recent new data led to a reevaluation of structural relationships between phenethylamine and indole, or tryptamine, hallucinogens. A new hypothesis is developed which may reflect requirements for binding at central serotonin receptors. In particular, it is hypothesized that the 2, 4 and 5 substituents of phenethylamines correspond approximately to the 2, 6 and 5 positions, respectively, of the indole nucleus in tryptamines. In order further to test this concept, it is proposed to study the relative binding orientation of the aromatic substituents of phenethylamine hallucinogens by synthesis and biological evaluation of the R,R and S,R diastereomers of 2,alpha dimethyl-1,3-benzodioxole-5-ethanamine. Second, the absolute configuration for these diastereomers will be determined using X-ray crystallography. Also, it is proposed to use X-ray crystallography to determine the absolute configuration of trans-2-(2,5-dimethoxy-4-methylphenyl)-cyclopropyl amine, since this investigator has found that the (-) isomer shows stereoselective hallucingoen-like activity. Also proposed is the development of an asymmetric synthesis for isomers of 5-methoxy and 5-ethoxy-alpha-methyltryptamine. Results of testing the proposed compounds should lead to definite conclusions about the stereochemistry involved in hallucinogen binding. This information may be extrapolated to define requirements for binding at central serotonin receptors.